HIV-1 infected patients receiving long-term therapy with lamivudine or emtricitabine (nucleoside reverse transcriptase inhibitors [NRTIs]) are at risk for the development of a mutation at position M184 on the HIV reverse transcriptase gene. This mutation confers resistance to both drugs (> 100 fold increase in IC50).

In-vitro studies with elvucitabine have shown that HIV-1 isolates with the M184V mutation show only a 10-fold increase in IC50 as compared to wild type HIV-1. Achillion Pharmaceutical's intention is to demonstrate that 10 mg of elvucitabine, administered once per day for 14 days with continued background anti-HIV-1 medications, will demonstrate a fall in HIV-1 RNA plasma levels, as compared to baseline. The data from this study will guide dosing in future long-term studies in HIV-1 infected patients with the M184V mutation.

To demonstrate the antiviral activity of 10 mg of elvucitabine administered QD for 14 days in combination with background antiretroviral therapy as compared with lamivudine in combination with background antiretroviral therapy in HIV-1 infected subjects with a documented M184V variant

To assess the safety of elvucitabine therapy in HIV-1 infected subjects with a documented M184V variant Number of Subjects: 20 Number of Study Centers: Multi-center study Study Population: HIV-1 infected subjects who are presently failing an antiretroviral therapy regimen containing lamivudine or emtricitabine, genotypically demonstrate a MI84V variant, and have an HIV RNA plasma level ≥ 2,000 and ≤ 150,000 copies/mL. Study Design: HIV-1 infected subjects, with a documented M184V variant, will be randomized to receive elvucitabine 10 mg QD or lamivudine 300 mg QD for 14 days. Subjects must be receiving a stable antiretroviral regimen (defined as no change in antiretroviral therapy for at least 4 weeks prior to randomization) that includes lamivudine or emtricitabine. At 72 hours prior to randomization, only lamivudine or emtricitabine will be stopped for washout; subjects will continue to receive the other drugs in their prescribed regimen (background antiretroviral therapy) during the 72-hour washout period. Subjects will then be randomized to receive blinded elvucitabine or lamivudine in a 1:1 ratio and continue to receive their prescribed background antiretroviral therapy for 14 days on an outpatient basis. Subjects will be followed for an additional 14 days post-treatment for safety, unless they enroll into the ACH443-018 extension study where they will continue to be treated and followed for safety.

Eligibility

Ages Eligible for Study:

18 Years to 65 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Clinically stable HIV-1 infected patients

Ages > 18 and < 65 years

Documented M184V mutation

CD4 cell count > 100 cells/mL

Plasma HIV-1 RNA levels > 5000 and < 150,000 copies/mL

Currently receiving lamivudine or emtricitabine

Other hematologic and metabolic parameters must be met.

Provide written informed consent

Other inclusion criteria apply.

Exclusion Criteria:

Hepatitis B antigen positive

HIV-1 genotype positive for more than or equal to 4 protease mutations

HIV-1 genotype positive for more than or equal to 2 non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations

Previous therapy with cytotoxic or myelosuppressive drugs in the past 3 months

Evidence or history of cirrhosis

Women who are pregnant or breast feeding

Other exclusion criteria apply.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00312039

Locations

United States, Alabama

UAB Birmingham

Birmingham, Alabama, United States, 35294

United States, California

University of California at Davis

Sacramento, California, United States, 95817

United States, Florida

University of Miami School of Medicine

Miami, Florida, United States, 33136

Orlando Immunology Center

Orlando, Florida, United States, 32803

Olayemi Osiyemi

West Palm Beach, Florida, United States, 33401

United States, Georgia

ACRA

Atlanta, Georgia, United States, 30308

United States, New York

Beth Israel Medical Center

New York, New York, United States, 10003

United States, Ohio

University of Cincinnati

Cincinnati, Ohio, United States, 45242

Sponsors and Collaborators

Achillion Pharmaceuticals

Investigators

Principal Investigator:

Judith Feinberg, MD

University of Cincinnati College of Pharmacy, Cincinnati, OH

Principal Investigator:

Donna Mildvan, MD

Beth Israel Medical Center, Infectious Diseases, Baird Hall, NY, NY

Principal Investigator:

Richard Pollard, MD

UC Davis Medical Center, Div. of Infectious Diseases, Sacramento, CA

Principal Investigator:

Michael Saag, MD

UAB Medical Center, AIDS Outpatient Clinic, Birmingham, AL

Principal Investigator:

Dushyantha Jayaweera, MD

University of Miami School of Medicine, Infectious Disease Research Unit, Miami, FL